Diabetes is an international health concern with millions of patients worldwide. There is an unmet need to develop a biosensor technology that is a fast and convenient way to continuously monitor blood glucose levels in diabetics. The proposed work seeks to develop an implantable glucose biosensor which can monitor glucose levels over a long period of time (3-6 months). The proposed implanted glucose biosensor design is distinctively different compared to existing continuous glucose monitoring devices (which have a disappointing lifetime of 3-7 days) and is expected to result in improved long-term efficacy. The innovative aspects of the proposed implantable glucose biosensor includes: (1) a self-cleaning membrane, (2) a fluorescent glucose sensing assay which is contained in the membrane to form the biosensor and (3) an end-use biosensor design which enables complete subcutaneous dwelling and convenient glucose monitoring by the patient. Membrane biofouling is considered to be the leading cause of failure for in vivo biosensors. The proposed self-cleaning membrane is distinct in its approach to control biofouling; it is designed to display active self-cleaning as a result of its thermoresponsive nature. The membrane will be based on a thermoresponsive nanocomposite hydrogel which is thermally cycled via an external heating source. This membrane will be used to house a glucose sensing assay which has been shown to have a larger dynamic range for physiologic glucose levels versus other optical fluorescent glucose sensing methods. Finally, the membrane and sensing assay will be combined to form a biosensor with a cylindrical geometry (expected dimensions of <5 mm diameter and <10 mm length) which permits a convenient end-use design for implantation, replacement and patient glucose monitoring. Ultimately, after injection into the subcutaneous tissue of the wrist, a watch device worn over the implanted biosensor site would contain the optical probe for non-invasive continuous glucose sensing and as well as the thermal heating element for membrane cleaning (i.e. thermal cycling). The multidisciplinary team of Drs. Grunlan, Cote, Clubb and Pishko and the facilities at Texas A&M University will enable the successful completion of the proposed research. The team brings the expertise to develop the proposed membrane and biosensors and conduct the in vitro and in vivo analysis.